SFEBES2018 Poster Presentations Diabetes & cardiovascular (27 abstracts)
Canagliflozin attenuates the progression of atherosclerosis and inflammation process in APOE knockout mice
Georgios K Dimitriadis 1, , Narjes Nasiri-Ansari 3 , Georgios Agorogiannis 4 , Despoina Perrea 5 , Ioannis D Kostakis 6 , Athanasios G Papavassiliou 3 , Gregory Kaltsas 1 , Eva Kassi 7, & Harpal S Randeva 2,
1Human Metabolism Research Unit, WISDEM Centre, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK; 2Division of Translational and Experimental Medicine, Warwick Medical School, University of Warwick, Coventry, UK; 3Department of Biological Chemistry, National and Kapodistrian University of Athens Medical School, Athens, Greece; 4Laboratory of Pathological Anatomy, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 5Laboratory for Experimental Surgery and Surgical Research ‘N.S. Christeas’, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 6Second Department of Propedeutic Surgery, National and Kapodistrian University of Athens, Medical School, ‘Laiko’ General Hospital, Athens, Greece; 7First Department of Internal Medicine, Laiko Hospital, Department of Biological Chemistry, National and Kapodistrian University of Athens, Athens, UK; 8Department of Biological Chemistry, National and Kapodistrian University of Athens Medical School, Athens, UK; 9Human Metabolism Research Unit, WISDEM Centre, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, Greece.
Sodium glucose co-transporter2 (SGLT2) inhibitors reduce the incidence of cardiovascular events in patients with Type 2 Diabetes Mellitus (T2DM) based on the results of recent cardiovascular outcome studies. Herein, we investigated the effects of long-term treatment with canagliflozin on biochemical and immunohistochemical markers related to atherosclerosis and atherosclerosis development in the aorta of Apolipoprotein E knockout (Apo-E(−/−)) mice. After 5 weeks of intervention, animals were sacrificed, and heart and aorta root sections were incubated with primary antibodies against MCP-1, CD68, a-smooth muscle actin, MMP-2, MMP-9, TIMP-1 and TIMP-2. Histomorphometry and immunohistochemistry were carried out while q-PCR experiments were performed to quantify mRNA expression. Canagliflozin-group had lower total-cholesterol, triglycerides and glucose levels (P<0.01), while heart rate was significantly lower (P<0.05). Histomorphometry revealed that one in seven Cana-group mice versus four in six control mice developed atheromatosis, while aortic root plaque was significantly less, and collagen was 1.6 times more intense in Canagliflozin-group suggesting increased plaque stability. Immunohistochemistry revealed that MCP-1 was significantly less expressed (P<0.05) in the aortic root of Canagliflozin-group treated mice while reduced expression of a-actin and CD68 was not reaching significance (P=0.15). VCAM-1 and MCP-1 mRNA levels were lower (P=0.02 and P=0.07, respectively), while TIMP-1/MMP-2 ratio expression was higher in Canagliflozin-group trending towards statistical significance (P=0.07). Canagliflozin attenuates the progression of atherosclerosis, reducing i) hyperlipidemia and hyperglycemia, and ii) inflammatory process, by lowering the expression of inflammatory molecules such as MCP-1 and VCAM-1. Moreover, Canagliflozin was found to increase the atherosclerotic plaque stability via increasing TIMP-1/MMP-2 ratio expression.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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